B7-h3 antibody and use thereof

Abstract

A B7-H3 antibody and a use thereof are provided. The heavy chain complementarity determining regions of the B7-H3 antibody include the amino acid sequences shown in SEQ ID NOs. 6-8, and the light chain complementarity determining regions of the B7-H3 antibody include the amino acid sequences shown in SEQ ID NOs. 14-16. The B7-H3 antibody can bind to a B7-H3 antigen and/or cells expressing the B7-H3 antigen. A B7-H3×CD3 bispecific antibody is constructed by using the B7-H3 antibody.

1 . A B7-H3 antibody, wherein heavy chain complementarity determining regions of the B7-H3 antibody comprise amino acid sequences as set forth in SEQ ID Nos. 6-8; and
 light chain complementarity determining regions of the B7-H3 antibody comprise amino acid sequences as set forth in SEQ ID Nos. 14-16.   
     
     
         2 . The B7-H3 antibody according to  claim 1 , wherein heavy chain variable regions of the B7-H3 antibody comprise an amino acid sequence as set forth in SEQ ID No. 1; and
 light chain variable regions of the B7-H3 antibody comprise an amino acid sequence as set forth in SEQ ID No. 9.   
     
     
         3 .- 5 . (canceled) 
     
     
         6 . A bispecific antibody, wherein the bispecific antibody comprises two heavy chains and two light chains;
 the heavy chains comprise an anti-B7-H3 heavy chain and an anti-CD3 heavy chain; the anti-B7-H3 heavy chain comprises a heavy chain of the B7-H3 antibody according to  claim 1 ;   the light chains comprise an anti-B7-H3 light chain and an anti-CD3 light chain; the anti-B7-H3 light chain comprises a light chain of the B7-H3 antibody according to  claim 1 ;   the heavy chains bind to the light chains by disulfide bonds; and   the anti-B7-H3 heavy chain binds to the anti-CD3 heavy chain through disulfide bonds.   
     
     
         7 . The bispecific antibody according to  claim 6 , wherein a variable region of the anti-CD3 heavy chain comprises an amino acid sequence as set forth in SEQ ID No. 49; and
 a variable region of the anti-CD3 light chain comprises an amino acid sequence as set forth in SEQ ID No. 9.   
     
     
         8 . The bispecific antibody according to  claim 6 , wherein the bispecific antibody comprises an immunoglobulin Fab domain binding to the B7-H3, an immunoglobulin Fab domain binding to the CD3, and a heterodimeric Fc region;
 the immunoglobulin Fab domain binding to B7-H3 comprises a variable region VH and a constant region CH1 of the anti-B7-H3 heavy chain, and a variable region and constant region of the anti-B7-H3 light chain;   the immunoglobulin Fab domain binding to the CD3 comprises a variable region VH and a constant region CH1 of the anti-CD3 heavy chain, and a variable region and constant region of the anti-CD3 light chain; and   the heterodimeric Fc region comprises an Fc fragment linked to the anti-B7-H3 heavy chain and an Fc fragment linked to the anti-CD3 heavy chain.   
     
     
         9 . The bispecific antibody according to  claim 8 , wherein the Fc fragment linked to the anti-B7-H3 heavy chain comprises a human Fc fragment or a humanized Fc fragment. 
     
     
         10 . The bispecific antibody according to  claim 8 , wherein CH3 of the Fc fragment linked to the anti-B7-H3 heavy chain contains T394D, P395D, and P396D mutations. 
     
     
         11 . The bispecific antibody according to  claim 8 , wherein CH3 of the Fc fragment linked to the anti-CD3 heavy chain contains P395K, P396K, and V397K mutations. 
     
     
         12 . The bispecific antibody according to  claim 8 , wherein CH2 of the Fc fragment linked to the anti-B7-H3 heavy chain contains L234A, L235A, and P329G mutations. 
     
     
         13 .- 16 . (canceled) 
     
     
         17 . A method for treating diseases associated with a tumor, comprising administering to a subject in need thereof the B7-H3 antibody according to  claim 1 . 
     
     
         18 . The method for treating diseases associated with a tumor according to  claim 17 , wherein the tumor comprises any one or a combination of at least two selected from the group consisting of neurological system tumor, colorectal cancer, liver cancer, head and neck cancer, lung cancer, melanoma, pancreatic cancer, gastric cancer, kidney cancer, bladder cancer, breast cancer, ovarian cancer and prostate cancer. 
     
     
         19 . The bispecific antibody according to  claim 6 , wherein heavy chain variable regions of the B7-H3 antibody comprise an amino acid sequence as set forth in SEQ ID No. 1; and
 light chain variable regions of the B7-H3 antibody comprise an amino acid sequence as set forth in SEQ ID No. 9.   
     
     
         20 . The bispecific antibody according to  claim 7 , wherein the bispecific antibody comprises an immunoglobulin Fab domain binding to the B7-H3, an immunoglobulin Fab domain binding to the CD3, and a heterodimeric Fc region;
 the immunoglobulin Fab domain binding to B7-H3 comprises a variable region VH and a constant region CH1 of the anti-B7-H3 heavy chain, and a variable region and constant region of the anti-B7-H3 light chain;   the immunoglobulin Fab domain binding to the CD3 comprises a variable region VH and a constant region CH1 of the anti-CD3 heavy chain, and a variable region and constant region of the anti-CD3 light chain; and   the heterodimeric Fc region comprises an Fc fragment linked to the anti-B7-H3 heavy chain and an Fc fragment linked to the anti-CD3 heavy chain.   
     
     
         21 . The bispecific antibody according to  claim 9 , wherein CH3 of the Fc fragment linked to the anti-CD3 heavy chain contains P395K, P396K, and V397K mutations. 
     
     
         22 . The bispecific antibody according to  claim 10 , wherein CH3 of the Fc fragment linked to the anti-CD3 heavy chain contains P395K, P396K, and V397K mutations. 
     
     
         23 . The bispecific antibody according to  claim 9 , wherein CH2 of the Fc fragment linked to the anti-B7-H3 heavy chain contains L234A, L235A, and P329G mutations. 
     
     
         24 . The bispecific antibody according to  claim 10 , wherein CH2 of the Fc fragment linked to the anti-B7-H3 heavy chain contains L234A, L235A, and P329G mutations. 
     
     
         25 . The bispecific antibody according to  claim 11 , wherein CH2 of the Fc fragment linked to the anti-B7-H3 heavy chain contains L234A, L235A, and P329G mutations.